title: Role of endogenous hydrogen peroxide during angiotensin type 1 receptor blockers administration in pacing-induced metabolic coronary vasodilatation in dogs in vivo.
abstract: BACKGROUND
  We have previously demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in canine coronary microcirculation in vivo. However, the role of H2O2/EDHF during angiotensin type 1 receptor blockers (ARB) administration in metabolic coronary dilatation in vivo remains to be examined. We examined whether H2O2 during ARB administration is involved in pacing-induced metabolic coronary vasodilatation in dogs in vivo and if so, whether such beneficial effects of ARB administration acutely improve coronary vasodilatation in diabetes mellitus (DM).
  
  
  METHODS
  Canine subepicardial coronary small arteries (CSA,≥ 100 μm) and arterioles (CA, <100 μm) in left anterior descending artery area were continuously observed by an intravital microscope under cyclooxygenase blockade(ibuprofen, 12.5 mg/kg, intravenous infusion, iv). Experiments were performed during paired right ventricular pacing under the following 4 conditions (n=5 each); (i) control, (ii) DM(alloxan 40 mg/ kg, iv, 1 week prior to study), (iii) DM+ARB(olmesartan, 10 μg/kg/min, 10 min, intracoronary infusion,ic)+L-NMMA (NOS inhibitor, 2 !mol/min, ic) and (iv)DM+ARB+catalase (H2O2 discomposer, 1000 U/ml, 5 min, ic).
  
  
  RESULTS
  Cardiac tachypacing (60 to 120 bpm) caused coronary vasodilatation in both-sized arteries under control conditions. DM significantly decreased the vasodilatation compared with control in CSA and there was a residual vasodilatation for the loss of NO in CA, whereas DM+ARB+L-NMMA improved the vasodilatation compared with DM alone in CA and was significantly decreased by DM+ARB+catalase in CA.
  
  
  CONCLUSIONS
  These results indicate that H2O2 during ARB administration is involved in pacing-induced metabolic coronary vasodilatation in DM in vivo and that there are substantial compensatory interactions between NO and H2O2.
authors.forename: Toyotaka
authors.initials: T
authors.lastname: Yada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Hiramatsu
authors.forename: Masami
authors.initials: M
authors.lastname: Goto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ogasawara
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kajiya
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000496:Alloxan / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D002374:Catalase / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001685:Biological Factors; D007093:Imidazoles; D013777:Tetrazoles; C067410:endothelium-dependent hyperpolarization factor; D019323:omega-N-Methylarginine; D000496:Alloxan; D000080242:8-Hydroxy-2'-Deoxyguanosine; C437965:olmesartan; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D007052:Ibuprofen